Orally administered moxifloxacin prolongs QTc in healthy Chinese volunteers: a randomized, single-blind, crossover study

Abstract

Aim: To investigate the QT/QTc effects of orally administered moxifloxacin in healthy Chinese volunteers.

Methods: This was a single-blinded, randomized, single-dose, placebo-controlled, two-period cross-over study. A total of 24 healthy Chinese volunteers were enrolled, randomly assigned to two groups: one group received moxifloxacin (400 mg, po) followed by placebo with a 7-d interval, another group received placebo followed by moxifloxacin with a 7-d interval. On the days of dosing, 12-lead 24 h Holter ECGs were recorded and evaluated by an ECG laboratory blind to the treatments. Blood samples were collected to determine plasma concentrations of moxifloxacin.

Results: The orally administered moxifloxacin significantly prolonged the mean QTc at all time points except 0.5 h post-dose. The largest time-matched difference in the QTcI was 8.35 ms (90% CI: 5.43, 11.27) at 4 h post-dose. The peak effect on QTcF was 9.35 ms (90% CI: 6.36, 12.34) at 3 h post-dose. A pharmacokinetic-QTc model suggested a 2.084 ms increase in the QTc interval for every 1000 ng/mL increase in plasma concentration of moxifloxacin. In addition, the orally administered moxifloxacin was well tolerated by the subjects.

Conclusion: Orally administered moxifloxacin significantly prolongs QTc, which supports its use as a positive control in ICH-E14 TQT studies in Chinese volunteers.

Figure 1

The placebo-adjusted QTcI change from baseline (CFB) following oral administration of 400 mg moxifloxacin in 24 healthy Chinese subjects. Data were subjected to an analysis of variance. The error bars represent 90% (two-sided) confidence intervals.

Figure 2

The mean plasma concentration versus time following the oral administration of 400 mg moxifloxacin in 24 healthy Chinese subjects. The error bars denote±1 SD.

Figure 3

The observed data and predicted placebo-corrected QTcI CFB mean values of the plasma concentration following oral administration of 400 mg moxifloxacin in 24 healthy Chinese subjects. Vertical lines indicate the mean C_max. CFB, change from baseline.